Gene-therapeutic methods that are currently known are based on the transfection of cells with DNA-constructs encoding for a desired gene product, mostly a therapeutically effective protein. Methods that are used hereby are usually adapted to in vitro methods. A targeted, i.e. selective, transfection of specific cell types without a prior isolation of the cells from their natural environment can not be realized with most of the methods of the state of the art, such as, for example, electroporation or liposome transfection.
Methods for a tissue specific DNA-transfer in vivo so far rely on viral transfer systems. Nevertheless, due to the potential danger of recombination with cellular sequences, these bear a safety risk that can hardly be calculated. A repeated in vivo-application of adenoviruses and adeno-associated viruses, the systems that are currently preferred for the transport of therapeutic genes, is impossible because of their high immunogenicity in most patients. In addition, due to the complex structure of the adenovirus and the structure of the adenoviral genome it is only possible with considerable effort to provide therapeutic DNA at the target site to a sufficient extent and in a suitable form.
Particularly in view of an undesired recombination and the associated danger to permanently modify the genome, gene-therapeutic methods could not be considered for the treatment of transiently occurring disease states, such as, for example, acute infections. Non-viral systems, such as, for example, liposomes and DNA-condensating molecules, indeed avoided these disadvantages, but, in turn, similar to retroviral systems exhibited much lower transfer efficiencies and target cell specificities.
Therefore, there is a need to provide clinically applicable gene-therapeutic compositions and methods, in order to avoid these problems.